Triethylamine → 2-[4-tert-Butyl-2-(piperidine-1-ylmethyl)phenoxy]-N-((1R)-1-{3-methyl-4-[(methylsulfonyl)amino]phenyl}ethyl)acetamide

HRID 1350858Notes

Reaction equation

HRID 1350858 reaction equation
[C:1]([C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][C:11](O)=[O:12])=[C:7]([CH2:16][N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:24][C@@H:25]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[C:29]([CH3:38])[CH:28]=1)[CH3:26].Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:1]([C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][C:11]([NH:24][C@@H:25]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[C:29]([CH3:38])[CH:28]=2)[CH3:26])=[O:12])=[C:7]([CH2:16][N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21097492[4-Tert-butyl-2-(piperidin-1-ylmethyl)phenoxy]acetic acidHCID 21097519N-{4-[(1R)-1-aminoethyl]-2-methylphenyl)methanesulfonamide hydrochloride

Product 1

HCID 117062362-[4-tert-Butyl-2-(piperidine-1-ylmethyl)phenoxy]-N-((1R)-1-{3-methyl-4-[(methylsulfonyl)amino]phenyl}ethyl)acetamideYield 5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent2×

Procedure

To a methylene dichloride (5.0 ml) solution of [4-tert-butyl-2-(piperidin-1-ylmethyl)phenoxy]acetic acid (111 mg) and N-{4-[(1R)-1-aminoethyl]-2-methylphenyl}methanesulfonamide hydrochloride (97 mg, 0.37 mmol), a portion of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (109 mg, 0.57 mmol), triethylamine (0.2 ml, 1.4 mmol), and catalytic amount of 4-(dimethylamino)pyridine were added at ambient temperature under nitrogen atmosphere. After being stirred for 18 hours, the reaction mixture was diluted with methylene dichloride and quenched with saturated aqueous solution of ammonium chloride. The organic layer was then washed with brine and dried over magnesium sulfate. After filtration to separate solvent and magnesium sulfate, the solvent was removed under reduced pressure, which was applied to an amino bound silica gel chromatography column and eluted with methylene dichloride/methanol=40/1 to give oil which contained 4-(dimethylamino)pyridine. This crude product was purified by HPLC gradient from 0.05% aqueous solution of ammonium formate/acetonitrile=4/96 to 96/4 to furnish 9.1 mg (5% yield) of the title compound as a white solid.

Workup

  1. customquenched with saturated aqueous solution of ammonium chloride
  2. washThe organic layer was then washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationAfter filtration
  5. customto separate solvent and magnesium sulfate
  6. customthe solvent was removed under reduced pressure, which
  7. washeluted with methylene dichloride/methanol=40/1
  8. customto give oil which
  9. customThis crude product was purified by HPLC gradient from 0.05% aqueous solution of ammonium formate/acetonitrile=4/96 to 96/4

Sources & evidence

ORD record
ord-1dcaeda8621a4dc5ab926b35002e5179
Source dataset
uspto-grants-2007_05
Patent number
US07214824B2

Reaction notes

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